A mixture of compounds, or analytes, can be separated by pumping the mixture through a separating device such as a chromatographic column. The outflow from the column may continue for perhaps several minutes, during which analytes of different molecular weights flow out at different times. Each analyte may flow out for a period such as a fraction of a minute. The analytes are delivered to a receiver where each analyte is stored in a separate container. At the same time as the column output is flowed to the receiver, a small amount of the column outlet is flowed to a mass spectrometer which indicates the molecular weight of each analyte. A prime use for the invention is to facilitate the purification of a synthesized compound during the development of a new drug. The products of the synthesis includes the desired synthesized compound (whose molecular weight is known), reactants and side products, all of which can be referred to as analytes.
In order for the mass spectrometer to function optimally, there should be a controlled low mass rate of analyte flowing into it. Such mass or flow rates should be easily adjustable and closely controllable despite variations in the flow rate of fluid passing through the column. The flow rate should be reproducibly controlled, which makes it easier for the mass spectrometer to unambiguously identify the collection vessel in which the desired synthesized compound should reside. It should be possible to select a desired carrier fluid to pump a predetermined volume, or fraction, of the analyte into the mass spectrometer, where the carrier fluid is different from the mobile phase used to pump the synthesized compound through the column. This is important because certain mobile phase fluids used in chromatographic columns contain dissolved buffer salts which can cause fouling of the mass spectrometer, and certain organic components of the mobile phase can inhibit optimum ionization of the analytes which is required in a mass spectrometer. In addition, the analyte mass transfer rate into the mass spectrometer should be very small, and generally should be a small fraction of the total analyte flow rate through the column. The analyte mass rates that flow from a preparative chromatographic column are inherently large, but the mass spectrometer does not tolerate a large analyte mass rate. A large mass rate can result in a lingering or tailing signal that distorts the results of a mass spectrometer, and a large mass rate can change the dielectric properties of the system and cause a momentary loss of signal.
Thus, a device that could separate out a very small but closely controlled portion of a large primary stream for flow of the portion along a secondary path, would be of value.